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The Journal of Neuroscience, October 25, 2006, 26(43):11120-11130; doi:10.1523/JNEUROSCI.3264-06.2006

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Development/Plasticity/Repair
Olfactory Ensheathing Cells Do Not Exhibit Unique Migratory or Axonal Growth-Promoting Properties after Spinal Cord Injury

Paul Lu,^1,2 Hong Yang,¹ Maya Culbertson,¹ Lori Graham,¹ A. Jane Roskams,³ and Mark H. Tuszynski^1,2

¹Department of Neuroscience, University of California at San Diego, La Jolla, California 92093, ²Veterans Affairs Medical Center, San Diego, California 92161, and ³Department of Zoology, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z4

Correspondence should be addressed to Mark H. Tuszynski, Department of Neuroscience, University of California at San Diego, La Jolla, CA 92093-0626. Email: mtuszynski{at}ucsd.edu

Olfactory ensheathing cells (OECs) have been reported to migrate long distances and to bridge lesion sites, guiding axonal regeneration after spinal cord injury (SCI). To understand mechanisms of OEC migration and axonal guidance, we injected lamina propria OECs 1 mm rostral and caudal to C4 SCI sites. One month later, OECs formed an apparent migrating cell tract continuously extending from the injection site through the lesion, physically bridging the lesion. Confocal immunolabeling demonstrated that, whereas this cell tract displaced host astrocytes, descending or ascending long tract axons did not preferentially extend into the cell tract and OECs failed to support bridging of corticospinal axons. Notably, the "bridging" tract of OECs formed within 1 h of cell injection, raising the possibility that cells passively spread from the pressure injection site rather than actively migrating. Control injections of bone marrow stromal cells (MSCs) or fibroblasts 1 mm from the lesion site also rapidly dispersed into the lesion cavity. Cell tracts extending into the lesion site were not seen when cells were injected either at low volumes, into spinal cord gray matter, or 3 d before or 9 d after SCI. OECs proliferated in injection sites, cell tracts, and lesion sites, indicating that OECs can also accumulate through cell proliferation. Thus, OECs do not appear to exhibit significant migratory properties when grafted to the spinal cord, exhibit no detectable difference in promoting axon growth into a SCI site compared with MSCs or fibroblasts, and do not support bridging of corticospinal axons beyond a dorsal column lesion.

Key words: olfactory ensheathing cells; spinal cord injury; migration; axon growth; axon guidance; proliferation

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Received July 28, 2006; accepted Sept. 17, 2006.

Correspondence should be addressed to Mark H. Tuszynski, Department of Neuroscience, University of California at San Diego, La Jolla, CA 92093-0626. Email: mtuszynski{at}ucsd.edu

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